Variation at the NFATC2 Locus Increases the Risk of Thiazolidinedione-Induced Edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) Study

被引：30

作者：

Bailey, Swneke D. ^{[1
]}

Xe, Changchun ^{[2
,3
]}

Do, Ron ^{[1
]}

Montpetit, Alexandre ^{[4
]}

Diaz, Rafael ^{[5
]}

Mohan, Viswanathan ^{[6
]}

Keavney, Bernard ^{[7
]}

Yusuf, Salim ^{[2
,3
,8
]}

Gerstein, Hertzel C. ^{[2
,3
,8
]}

Engert, James C. ^{[1
,9
]}

Anand, Sonia ^{[2
,3
,8
]}

机构：

[1] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[2] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada

[3] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada

[4] Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[5] Estudios Clin Latino Amer, Rosario, Jujuy, Argentina

[6] Madras Diabet Res Fdn, Madras, Tamil Nadu, India

[7] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England

[8] McMaster Univ, Dept Med, Hamilton, ON, Canada

[9] McGill Univ, Dept Med, Montreal, PQ, Canada

来源：

DIABETES CARE | 2010年 / 33卷 / 10期

基金：

加拿大健康研究院;

关键词：

CARDIAC-HYPERTROPHY; TYPE-2; GLUCOSE; GENE;

D O I：

10.2337/dc10-0452

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

OBJECTIVE - Thiazolidinediones are used to treat type 2 diabetes. Their use has been associated with peripheral edema and congestive heart failure outcomes that may have a genetic etiology. RESEARCH DESIGN AND METHODS - We genotyped 4,197 participants of the multiethnic DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial with a 50k single nucleotide polymorphisms (SNP) array, which captures 2000 cardiovascular, inflammatory, and metabolic genes. We tested 32,088 SNPs for an association with edema among Europeans who received rosiglitazone (n = 965). RESULTS - One SNP, rs6123045, in NFATC2 was significantly associated with edema (odds ratio 1.89 [95% CI 1.47-2.42]; P = 5.32 x 10(-7), corrected P = 0.01.7). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 x 10(-4)) when compared with individuals homozygous for the protective allele, with heterozygous individuals having an intermediate risk. The interaction between the SNP and rosiglitazone for edema was significant (P = 7.68 x 10(-3)). Six SNPs in NEATC2 were significant in both Europeans and Latin Americans (P < 0.05). CONCLUSIONS - Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone.

引用

页码：2250 / 2253

页数：4

共 15 条

[1]

Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes - A 6-month randomized placebo-controlled dose-response study [J].